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A nanoparticle-coupled T2 peptide induces immune tolerance and ameliorates chronic prostatitis/chronic pelvic pain
Yanfang Cao1, Yijie Cheng1, Awais Ullah Ihsan1
1Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, 211198, China.
Abstract:
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease of unclear etiology. Precise treatment of CP/CPPS is not available due to lack of specific cause; however, autoimmunity is the most valid theory. We develop a new treatment strategy that involves synthesis and coupling of biodegradable nanoparticles to antigenic T2 peptide to induce immune tolerance in CP/CPPS mice models. A total of 50 male C57BL/6 mice were randomized into five groups, that is, naïve, Model, PLGA-PEMA, PLGA-PEMA-OVA323-339 , and PLGA-PEMA-T2 group. All groups except naïve were injected subcutaneously on day 0 with 0.2 mL of T2 peptide with CFA to generate valid CP/CPPS models. After successful induction of CP/CPPS, Model group, PLGA-PEMA, PLGA-PEMA-OVA, and PLGA-PEMA-T2 groups were treated with 0.15 mL of normal saline, 0.2 mg of PLGA-PEMA and PLG-PEMA-T2 and 0.3 mg PLGA-PEMA-OVA nanoparticles, respectively, on day 28. Hematoxylin and eosin staining, and ELISA were used to evaluate the variation in CP/CPPS manifestations and seral level of IL-10 in each group. Pain threshold and voiding behavior were also recorded for every group. Mice treated with PLGA-PEMA-T2 exhibited enhanced pain threshold, reduced urine frequency, and prostate pathology. Furthermore, serum level of inflammatory mediators (TNF-α and CRP) were reduced and anti-inflammatory IL-10 was enhanced in PLGA-PEMA-T2 group as compared to other groups. Our results demonstrate that PLGA-PEMA-T2 nanoparticle ameliorates disease manifestations in CP/CPPS mice models and upregulates IL-10 which is essential for tolerance induction. This strategy highlights the new therapeutic approach utilizing biodegradable nanoparticles for the treatment of CP/CPPS.
Insights
Biodegradable nanoparticles coupled with T2 peptide show promise for treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This novel approach may induce immune tolerance, reducing inflammation and improving symptoms in CP/CPPS mouse models.
Area of Science:
- Immunology
- Nanotechnology
- Urology
Background:
- Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition with unclear causes, hindering effective treatment.
- Autoimmunity is considered the most plausible etiological theory for CP/CPPS.
- Current treatment strategies for CP/CPPS lack specificity due to the absence of a defined cause.
Purpose of the Study:
- To develop and evaluate a novel treatment strategy for CP/CPPS using biodegradable nanoparticles conjugated with an antigenic peptide.
- To investigate the potential of inducing immune tolerance as a therapeutic approach for CP/CPPS.
- To assess the efficacy of PLGA-PEMA-T2 nanoparticles in ameliorating CP/CPPS manifestations in a mouse model.
Main Methods:
- Biodegradable nanoparticles (PLGA-PEMA) were synthesized and coupled with the T2 peptide.
- CP/CPPS mouse models were established by subcutaneous injection of T2 peptide and Complete Freund's Adjuvant (CFA).
- Mice were treated with PLGA-PEMA-T2 nanoparticles, and outcomes were assessed using histological analysis, ELISA, pain threshold measurements, and voiding behavior observation.
Main Results:
- Mice treated with PLGA-PEMA-T2 nanoparticles demonstrated improved pain thresholds and reduced urinary frequency.
- Prostate pathology was significantly ameliorated in the PLGA-PEMA-T2 treated group.
- Treatment with PLGA-PEMA-T2 nanoparticles led to decreased levels of inflammatory mediators (TNF-α, CRP) and increased levels of the anti-inflammatory cytokine IL-10.
Conclusions:
- The developed PLGA-PEMA-T2 nanoparticle strategy effectively ameliorates CP/CPPS disease manifestations in a mouse model.
- This therapeutic approach successfully upregulates IL-10, a key cytokine for inducing immune tolerance.
- The use of biodegradable nanoparticles represents a promising new therapeutic avenue for the treatment of CP/CPPS.
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